RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known whether four-drug combination chemotherapy is more effective than two-drug combination chemotherapy in treating bladder cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of two combination chemotherapy regimens in treating patients who have bladder cancer.

Condition	Treatment or Intervention	Phase
stage III bladder cancer childhood kidney/urinary cancer transitional cell carcinoma of the bladder urethral cancer associated with invasive bladder cancer	Drug: carboplatin  Drug: cisplatin  Drug: doxorubicin  Drug: methotrexate  Drug: paclitaxel  Drug: vinblastine	Phase III

Further Study Details: 

OBJECTIVES: I. Compare the recurrence rates and overall survival of patients treated with postoperative adjuvant methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) to those treated with combination paclitaxel and carboplatin for muscle invasive bladder cancer at particularly high risk of relapse. II. Compare the relative toxicities of postoperative M-VAC versus those encountered with postoperative paclitaxel and carboplatin. III. Compare the quality of life scores during and following completion of treatment of patients in these two treatment arms.

PROTOCOL OUTLINE: This is a randomized study. Patients are stratified by N stage (N0 vs N+) and performance status (0-1 vs 2). Patients are randomized to receive methotrexate, vinblastine, doxorubicin, and cisplatin (arm I) or paclitaxel and carboplatin (arm II). Arm I: Patients receive methotrexate IV push on days 1, 15, and 22; vinblastine IV push on days 2, 15, and 22; doxorubicin IV push on day 2; and cisplatin IV over 2 hours on day 2. Treatment repeats every 28 days for 4 courses. Arm II: Patients receive paclitaxel IV over 3 hours on days 1 followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses. Quality of life assessments are completed pretreatment, prior to course 3, 6 weeks after the last dose of chemotherapy, and at 6, 12, and 24 months from the end of therapy. Patients are followed every 3 months until year 2, every 6 months for years 2-5, and then annually thereafter.

PROJECTED ACCRUAL: There will be 490 patients accrued into this study within 2.6 years.

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed transitional cell carcinoma of the bladder or mixed histologies containing a component of transitional cell carcinoma
• Must have undergone radical cystectomy and pelvic lymph node dissection within 12 weeks prior to randomization; No evidence of distant metastatic disease on pre- or postoperative radiographic scans; No positive surgical margins in the cystectomy specimen and no known macroscopic residual disease left at time of cystectomy
• No bladder sparing surgery
• May have undergone continent urinary diversion or neobladder procedure but must have recovered completely from the effects of surgery
• Must have muscle-invasive disease on final pathologic staging and have a primary tumor stage of pT4, any N, M0, or any pT, N+, M0, or pT3b, any N, any M, and following a pelvic lymph node dissection have a pathologic nodal stage of pN0 (only if pT3b or pT4), pN1, or pN2
• Clinically unsuspected organ confined prostate cancer found during cystoprostatectomy allowed

--Prior/Concurrent Therapy--

• Recovered from all prior therapies
• Biologic therapy: No prior biologic response modifier therapy; No filgrastim (G-CSF) 24 hours pre- or post-chemotherapy administration
• Chemotherapy: No prior systemic chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: No prior radiotherapy as a component of bladder sparing therapy; No prior adjuvant radiotherapy for locally advanced disease with positive margins
• Surgery: See Disease Characteristics
• Other: Prior intravesical therapy for superficial bladder cancer allowed and recovered

--Patient Characteristics--

• Age: Any age
• Performance status: ECOG 0-2
• Life expectancy: Not specified
• Hematopoietic: WBC at least 3,500/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN); SGOT no greater than 2 times ULN
• Renal: Creatinine no greater than 1.7 mg/dL OR Creatinine clearance at least 60 mL/min
• Cardiovascular: No second degree atrioventricular block or bundle branch block
• Other: No history of prior malignancy in the past 5 years except basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix; No active infection requiring antibiotics; No history of allergic reaction to drugs utilizing the vehicle Cremophor; Not pregnant or nursing; Fertile patients must use effective contraception

Georgia
      Veterans Affairs Medical Center - Atlanta (Decatur), Decatur,  Georgia,  30033,  United States
Indiana
      Indiana University Hospitals, Indianapolis,  Indiana,  46202,  United States
New Jersey
      Fox Chase Cancer Center at Virtua-Memorial Hospital Burlington County, Mount Holly,  New Jersey,  08060,  United States
      Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States
      Hunterdon Regional Cancer Center, Flemington,  New Jersey,  08822,  United States
      Overlook Hospital, Summit,  New Jersey,  07902-0220,  United States
      Riverview Medical Center, Red Bank,  New Jersey,  07701,  United States
      South Jersey Hospital - Millville, Millville,  New Jersey,  08332,  United States
New York
      NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York,  New York,  10016,  United States
      Veterans Affairs Medical Center - New York, New York,  New York,  10010,  United States
Ohio
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States
Pennsylvania
      Hahnemann University Hospital, Philadelphia,  Pennsylvania,  19102-1192,  United States
Tennessee
      Vanderbilt Cancer Center, Nashville,  Tennessee,  37232-6838,  United States

Study chairs or principal investigators

Bruce J. Roth,  Study Chair,  Eastern Cooperative Oncology Group   

Study ID Numbers:  CDR0000066808; E-1897
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003701
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08